A Double-Blind Placebo-Controlled Clinical Evaluation of Multistem for the Treatment of Ischemic Stroke

Hess, David C.; Sila, Cathy A.; Furlan, Anthony J.; Wechsler, Larry; Switzer, Jeffrey A.; Mays, Robert W.

doi:10.1111/ijs.12065

Cited by 86 publications

(62 citation statements)

References 36 publications

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“…Multipotency and tissue support regulated by the niche environment make stem cells possess the ability for tissue regeneration [7,8]. Among stem cells, mesenchymal stem cells (MSCs) are known to be potent immune modulators [9] and their potential therapeutic benefits on acute, ischemic disorders such as acute myocardial infarction [10], stroke [11], traumatic brain injury [12], and acute liver failure [13] have been reported. Little is currently known about MSCs for acute, ischemic germ cell injury.…”

Section: Introductionmentioning

confidence: 99%

Local Injection of Mesenchymal Stem Cells Protects Testicular Torsion-induced Germ Cell Injury

Hsiao

Chang

et al. 2016

Cytotherapy

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Section: Introductionmentioning

confidence: 99%

Local Injection of Mesenchymal Stem Cells Protects Testicular Torsion-induced Germ Cell Injury

Hsiao

Chang

et al. 2016

Cytotherapy

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“…Experimental animal studies provide pre-clinical evidence regarding the safety and feasibility of the stem cell based reparative approach for ischemic stroke which has been vindicated during the clinical studies (12,13). The beneficial therapeutic outcome from the donor cells is considered as multifactorial that ranges from neurogenesis to the release of bioactive molecules as part of their paracrine activity to support the endogenous repair mechanisms in the damaged area of the brain (14,15).…”

Section: Original Articlementioning

confidence: 99%

Optimization of time for neural stem cells transplantation for brain stroke in rats

Ziaee¹,

Tabeshmehr²,

Haider³

et al. 2017

Stem Cell Investig.

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Background: Despite encouraging data in terms of neurological outcome, stem cell based therapy for ischemic stroke in experimental models and human patients is still hampered by multiple as yet un-optimized variables, i.e., time of intervention, that significantly influence the prognosis. The aim of the present study was to delineate the optimum time for neural stem cells (NSCs) transplantation after ischemic stroke. Methods:The NSCs were isolated from 14 days embryo rat ganglion eminence and were cultured in NSA medium (neurobasal medium, 2% B27, 1% N2, bFGF 10 ng/mL, EGF 20 ng/mL and 1% pen/strep). The cells were characterized for tri-lineage differentiation by immunocytochemistry for tubulin-III, Olig2 and GFAP expression for neurons, oligodendrocytes and astrocyte respectively. The NSCs at passage 3 were injected intraventricularly in a rodent model of middle-cerebral artery occlusion (MCAO) on stipulated time points of 1 & 12 h, and 1, 3, 5 and 7 days after ischemic stroke. The animals were euthanized on day 28 after their respective treatment.Results: dUTP nick end labeling (TUNEL) assay and Caspase assay showed significantly reduced number of apoptotic cells on day 3 treated animals as compared to the other treatment groups of animals. The neurological outcome showed that the group which received NSCs 3 days after brain ischemia had the best neurological performance. Conclusions:The optimum time for NSCs transplantation was day 3 after ischemic stroke in terms of attenuation of ischemic zone expansion and better preserved neurological performance.

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“…The Prasad trial delivered far lower numbers of cells than other trials of intravenous cells (eg 0.6-1.6 x10 8 cells in a bone marrow-derived MSC study 30 or 400-1200 million cells in the Athersys trial 39 ).…”

Section: The Acute or Early Subacute Paradigmmentioning

confidence: 99%

Clinical trial design for stem cell therapies in stroke: What have we learned?

Muir

2017

Neurochemistry International

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Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches -one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, antiapoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small singlearm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered.Introduction:

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A Double-Blind Placebo-Controlled Clinical Evaluation of Multistem for the Treatment of Ischemic Stroke

Abstract: If MultiStem is safe and there is a signal of efficacy, a late stage phase IIb-III trial is planned.

Cited by 86 publications

References 36 publications

Local Injection of Mesenchymal Stem Cells Protects Testicular Torsion-induced Germ Cell Injury

Local Injection of Mesenchymal Stem Cells Protects Testicular Torsion-induced Germ Cell Injury

Optimization of time for neural stem cells transplantation for brain stroke in rats

Clinical trial design for stem cell therapies in stroke: What have we learned?

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